Halogen containing ionone derivatives and compositions containing same

ABSTRACT

The present invention relates to novel compounds useful as fragrance materials which have the structure ##STR1## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond; R 1 , R 2  and R 3  are each the same or different and each represents hydrogen or methyl; and X is halogen. The invention also provides methods of preparing these compounds from readily available cyclohexene derivatives and fragrance compositions which include the compounds.

BACKGROUND OF THE INVENTION

There is an increased demand for materials which can be used to modify and/or enhance the organoleptic properties of consumable items. The natural oils which have traditionally been used for this purpose often suffer the disadvantages of irregular or limited supply, variable quality and high cost. Consequently the search for new and inexpensive chemicals which can be used as partial or total replacements for essential oils, or which can be used in the creation of new and unique flavor and fragrance materials has intensified in recent years.

The use of halogen containing compounds as fragrance materials is well documented. One example is gamma homocyclogeranyl chloride which has the general structure ##STR2## and is a component of tincture of Ambergris. 2-Chloro-3-methoxy-5-methylphenol and 2,4-dimethoxy-6-methyl chlorobenzene have been found in Evernia Prunastri. Further examples may be found in Actander, Perfume and Flavor Chemicals (1969). For example alphabromostyrol which has the structure ##STR3## is identified as compound No. 370 in Actander. Its fragrance is described therein as pungent-sweet, grassy-floral odor, reminiscent of Hyacinth in extreme dilution. Slightly softer than the odor of omega-Bromostyrol.

Actander compound No. 608 is 2-chloro-4,6-dinitro-1,3-dimethyl-5-tertiary-butylbenzene which has the structure ##STR4## and is described as having an odor similar to 2,4,6-trinitro-3-tertiary-butyl toluene, sweet, heavy, musky, slightly more pungent and less tenacious.

Actander compound No. 2272 is mononitro dibromobutylmeta-cresol methylether which has the structure ##STR5## and is described as having a sweet Ambergris musk-like odor of good tenacity.

SUMMARY OF THE INVENTION

In accordance with the present invention it has been found that compounds having the structure ##STR6## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond; R₁, R₂ and R₃ are each the same or different and each represents hydrogen or methyl, and X represents a halogen group are useful as fragrance materials.

The present invention also provides efficient and economical processes for preparing these compounds involving reacting a substituted cyclohexene derivative having the structure ##STR7## wherein the dashed line may be either a carbon-carbon single bond or a carbon carbon double bond and R₁, R₂ and R₃ are each the same or different and each represents hydrogen or methyl with a hypohalous acid having the formula HO-X wherein X is halogen.

Finally in accordance with the present invention it has been found that fragrance compositions can be prepared by incorporating in these compositions the novel compounds of this invention.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with this invention, there have been discovered novel halogen-containing cyclohexane derivatives as represented by the structure ##STR8## wherein the dashed line may either be a carbon-carbon single bond or a carbon-carbon double bond; R₁, R₂ and R₃ are each the same or different and each represents hydrogen or methyl; and X represents a halogen group have been prepared. It will be recognized that the chemicals of this invention can exist in several stereoisomeric forms. The foregoing structural formula is intended to embrace the individual stereoisomers, as well as mixtures of the various stereoisomers of the halogen compounds of this invention. The compounds exhibit clean, soft, powdery, warm, sweet, woody orris, berry-like notes rendering them useful in fine fragrances as well as perfumed products such as deodorants, cosmetic preparations and the like.

The compounds of this invention can be conveniently and inexpensively prepared by reacting a cyclohexene derivative having the structure ##STR9## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond and R₁, R₂ and R₃ are each the same or different and each represents hydrogen or methyl with a hypohalous acid having the general formula HO-X, where X is selected from a group consisting of the halogens chlorine, bromine or iodine, preferably chlorine or bromine in the presence of an organic solvent such as methylene dichloride, ethylene dichloride, hexane or toluene, preferably methylene dichloride or ethylene dichloride. The hypohalous acid is generated in situ in accordance with standard procedures (see H. O. House, "Modern Synthetic Reactions," 2nd ed., p. 434 (1972). Isolation and purification of the final products is achieved by conventional techniques including extraction, distillation, preparative chromatographic techniques and the like.

One or more of the halogen-containing cyclohexane derivatives of this invention and auxiliary perfume ingredients, for example, alcohols, aldehydes, ketones, nitriles, esters and essential oils may be admixed so that the combined odors of the individual components produce a desired fragrance. Such perfume compositions are carefully balanced, harmonious blends of essential oils, aroma chemicals, resinoids and other extracts of natural odorous materials. Each ingredient imparts its own characteristic effect to the composition. Thus, one or more of the halogen-containing compounds of this invention can be employed to impart novel characteristics into fragrance compositions.

Such compositions may contain up to about 80 weight percent of any one or more of the halogen containing cyclohexane derivatives of the invention. Ordinarily at least 0.001 weight percent of the halogen-containing cyclohexane derivative is required to impart significant odor characteristics. Amounts in the range of from about 1 to about 60 weight percent are preferred. The halogen-containing compounds of this invention may be formulated into concentrates containing about 1 to 60 weight percent of the chemical in an appropriate solvent. Such concentrates are then employed to formulate products such as colognes, deodorants, etc., wherein the concentration of the chemicals of this invention can be in the range of from about 0.001 to about 7 weight percent depending upon the final product.

A number of examples are provided hereinafter to illustrate the preferred embodiments of this invention, but are in no way meant to limit the scope thereof.

The following instrumentation was used to characterize the novel compounds of this invention. Nuclear Magnetic Resonance (NMR) spectra were recorded with a Varian Associates T-60A spectrometer using tetramethylsilane as the internal reference. Infrared (IR) spectra were obtained with a Perkin Elmer 710 B spectrophotometer. Mass spectra (MS) were obtained with a Hewlett-Packard 5985 Mass Spectrometer. Unless otherwise stated weights are in grams, temperatures are in degrees centigrade and pressures in mm Hg.

EXAMPLE 1 ##STR10##

To a mixture of commercial bleach (28.5 ml of a 5.25% solution of sodium hypochlorite) α-dihydro-ionone (3.88 g) and methylene chloride (110 ml) was added a solution of potassium phosphate (monobasic) (5.44 g) in water (40 ml) during a 15 minute period. The mixture was stirred for 1 hour at 25°. The methylene chloride solution was washed with sodium bicarbonate solution, the solvent evaporated, and the residue distilled to give 2.81 g (61% yield) of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl)-2-butanone, bp 101°-106°, 0.2 mm. NMR (CDCl₃) δ0.85 and 0.95 (6H,2s,>C(CH₃)₂), 0.9-2.6 (9H, m), 2.10 (3H, s, --COCH₃), 4.36-4.55 (1H, t, J=6 Hz,>CHCl), 4.76 and 5.33 (2H,2s,>C=(CH₂). IR (film) γmax 2950, 1720, 1675, 1650, 1455, 1360. MS m/e 193, 175, 159, 134, 119.

EXAMPLE 2

The reaction of α-dihydro-ionone and hypochlorous acid was carried out as described in Example 1 except that hexane was substituted for methylene chloride. A 59% yield of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl-2-butanone was obtained. The spectral data was identical to that reported in Example 1.

EXAMPLE 3 ##STR11##

A solution of sodium bromide (6.17 g) in water (10 ml) and commercial bleach (31.2 ml of a solution of sodium hypochlorite) were stirred together for 5 minutes and a solution of dihydro-α-ionone (3.88 g) in methylene chloride was added. Then a solution of potassium phosphate (monobasic) (5.44 g) in water (30 ml) was added during 30 minutes. After stirring for 50 minutes at 25° a solution of sodium bromide (2.05 g) and commercial bleach (10 ml) was added, followed by a solution of potassium phosphate (monobasic) (2.72 g) in water (10 ml) and the reaction mixture stirred for 15 minutes at 25°. The methylene chloride solution was washed with sodium bicarbonate solution and the solvent evaporated to provide the crude product (5.86 g). Column chromatography gave 1.87 g of 4-(5-bromo-6-methylene-2,2-dimethylcyclohexyl)-2-butanone. NMR (CDCl₃) δ0.93 (6H, s, >C(CH₃)₂), 0.9-2.6 (9H, m), 2.12 (3H, s, --COCH₃), 4.6-5.1 (1H, m, >CHBr), 4.76 and 5.28 (2H, 2s, >C═CH₂), 4.68 and 5.20 (2H, 2s, >C═CH₂, minor isomer; isomer ratio 3/1). IR (film) ν_(max) 2960, 1720, 1675, 1650, 1455, 1360.

EXAMPLE 4 ##STR12##

To a mixture of commercial bleach (42.6 ml of a 5.25% solution of sodium hypochlorite), α-irone (6.24 g), and methylene chloride (200 ml) was added a solution of potassium phosphate (monobasic) (8.16 g) in water (40 ml) during a 30 minute period. The mixture was stirred for 1 hour at 25°. The methylene chloride solution was washed with sodium bicarbonate solution and evaporated to give 7.3 g of crude product. Purification by column chromatography gave 4.59 g of 4-(5-chloro-6-methylene-2,2,3-trimethylcyclohexyl)-3-buten-2-one. NMR (CDCl₃) δ0.70-0.78 (2H, d, J=5 Hz, >CHCH₃), 0.90, 0.93 and 0.99 (6H, 3s, >C(CH₃)₂), 0.9-1.3 (1H, m, >CHCH₃), 1.5-2.1 (2H, m, --CH₂ --), 2.25, 2.26 and 2.28 (3H, 3s, --COCH₃), 2.67 and 2.83 (1H, 2s, >CH--CH═CH--), 4.6-4.9 (1H, m, >CHCl), 4.93 and 5.12 (2H, 2s, >C═CH₂, 5.8-6.3 (1H, m, --CH═CH--CO--), 6.6-7.6 (1H, m, --CH═CHCO--). IR (film) ν _(max) 2960, 1695, 1675, 1620, 1460, 1430 cm⁻¹. MS m/e 207, 163.

EXAMPLE 5 ##STR13##

To a mixture of commercial bleach (28.5 ml of a 5.25% solution of sodium hypochlorite), α-ionone (3.84 g), and methylene chloride (330 ml) was added a solution of potassium phosphate (monobasic) (5.44 g) in water (40 ml) during a 30 minute period. The mixture was stirred for 30 minutes at 25°, the methylene chloride solution washed with sodium bicarbonate solution and evaporated to give 4.1 g of crude product. Purification by column chromatography gave 2.35 g of 4-(5-chloro-6-methylene-2,2-dimethylcyclohexyl)-3-buten-2-one. NMR (CDCl₃) δ0.90 and 0.93 (6H, 2s, >C(CH₃)₂), 0.9-2.1 (4H, m), 2.27 (3H, s, --COCH₃), 2.53 and 2.71 (1H, 2s, >CH--CH═CH--), 4.35-4.68 (1H, m, >CHCl), 4.70, 4.83, 5.15 and 5.33 (2H, 4s, >C═CH₂), 5.9-6.4 (1H, m, --CH═CH--CO--), 6.7-7.3 (1H, --CH═CH--COCH₃). IR (film) ν_(max) 2960, 1695, 1675, 1630, 1450, 1430 cm.sup. -1. MS m/e 191, 149.

EXAMPLE 6

The following illustrates the utility of 4-(5-chloro-6-methylene-2,2-dimethyl-1-cyclohexyl)-2-butanone, the compound of Example 1, in a fantasy floral composition.

    ______________________________________                                         FANTASY FLORAL                                                                 pts/wt      Component                                                          ______________________________________                                         10          Oil Patchouly                                                      10          Eugenol Extra                                                      10          Geranyl Acetate                                                    10          Anisyl Acetate                                                     20          Iso Eugenol                                                        20          Hexyl Cinnamic Aldehyde                                            20          Hydroxy Citronellal                                                20          Oil Ylang Extra                                                    25          1% Sol. Aldehyde C-12 MNA in                                                   D.E.P. Odorless                                                    30          Geraniol                                                           30          Vetiveryl Acetate                                                  40          Phenyl Ethyl Alcohol                                               50          Coumarin                                                           50          Musk Ketone                                                        50          Oil Bergamot                                                       60          Oil Lemon                                                          70          Vanillin                                                           75          Compound of Example 1                                              100         Heliotropin Extra                                                  100         Benzyl Acetate                                                     100         Linalool                                                           100         Linalyl Acetate                                                    1000                                                                           ______________________________________                                    

EXAMPLE 7

The following illustrates the utility of 4-(5-bromo-6-methylene-2,2-dimethyl-1-cyclohexyl)-2-butanone, the compound of Example 3, in fragrance compositions of the fougere type.

    ______________________________________                                         FOUGERE                                                                        pts/wt     Component                                                           ______________________________________                                         20         Oil Vetiver Reunion                                                 20         10% Sol. Rose Oxide in D.E.P.                                                  Colorless                                                           20         Labdanum Resinoid Absolute                                          30         Coumarin                                                            30         10% Sol. Aldehyde C-11 in D.E.P.                                               Odorless                                                            30         Oil Patchouly                                                       30         Oil Geranium Maroc                                                  30         Citronellal Extra                                                   30         Geraniol                                                            30         Iso Amyl Salicylate                                                 30         Eugenol                                                             40         Linalool FCC                                                        50         Oil Lemon                                                           50         Oil Fir Needles Canadian                                            50         Linalyl Acetate                                                     50         Phenyl Ethyl Alcohol                                                50         Hexyl Cinnamic Aldehyde                                             100        Oil Lavandin Abrial Extra                                           100        Cedryl Acetate                                                      100        Compound of Example 3                                               110        Diethyl Phthalate                                                   1000                                                                           ______________________________________                                    

EXAMPLE 8

A fantasy woody floral fragrance may be prepared containing the compound of Example 4.

    ______________________________________                                         FANTASY WOODY FLORAL                                                           pts/wt     Component                                                           ______________________________________                                         60         Rhodinol Extra                                                      10         Phenylethyl Phenylacetate                                           100        Phenyl Ethyl Alcohol                                                50         Oil Rose Bulgarian                                                  30         Oil Ylang Extra                                                     40         Jasmin Absolute                                                     60         Linalool                                                            50         Benzyl Acetate                                                      140        Oil Vetiver Reunion                                                 50         Acetyl Cedrene                                                      30         10% Aldehyde C-11 in D.E.P.                                                    Odorless                                                            70         Musk Ketone                                                         40         Coumarin                                                            30         Amyl Cinnamic Aldehyde                                              130        Hydroxycitronellal                                                  110        Compound of Example 4                                               1000                                                                           ______________________________________                                     

What is claimed is:
 1. A compound defined by the generic structure ##STR14## wherein the dashed line may be either a carbon-carbon single bond or a carbon-carbon double bond; R₁, R₂ and R₃ are each the same or different and each represents hydrogen or methyl; and X is halogen.
 2. A compound in accordance with claim 1 wherein the dashed line represents a carbon-carbon single bond, R₁, R₂, and R₃ are hydrogen, and X is bromine.
 3. A compound in accordance with claim 1 wherein the dashed line represents a carbon-carbon single bond, R₁, R₂ and R₃ are hydrogen, and X is chlorine.
 4. A fragrance composition which comprises an amount of the compound of claim 1 effective to impart fragrance thereto in combination with conventional fragrance ingredients.
 5. A fragrance composition which comprises an amount of the compound of claim 2 effective to impart fragrance thereto in combination with conventional fragrance ingredients.
 6. A fragrance composition which comprises an amount of the compound of claim 3 effective to impart fragrance thereto in combination with conventional fragrance ingredients. 